Effects of calcitriol and paricalcitol on renal fibrosis in CKD

Laura Martínez-Arias, Sara Panizo, Cristina Alonso-Montes, Julia Martín-Vírgala, Beatriz Martín-Carro, Sara Fernández-Villabrille, Carmen García Gil-Albert, Carmen Palomo-Antequera, José Luis Fernández-Martín, María Piedad Ruiz-Torres, Adriana S. Dusso, Natalia Carrillo-López, Jorge B. Cannata-Andía, Manuel Naves-Díaz

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

BACKGROUND: In chronic kidney disease, the activation of the renin-angiotensin-aldosterone system (RAAS) and renal inflammation stimulates renal fibrosis and the progression to end-stage renal disease. The low levels of vitamin D receptor (VDR) and its activators (VDRAs) contribute to worsen secondary hyperparathyroidism and renal fibrosis. METHODS: The 7/8 nephrectomy model of experimental chronic renal failure (CRF) was used to examine the anti-fibrotic effects of treatment with two VDRAs, paricalcitol and calcitriol, at equivalent doses (3/1 dose ratio) during 4 weeks. RESULTS: CRF increased the activation of the RAAS, renal inflammation and interstitial fibrosis. Paricalcitol treatment reduced renal collagen I and renal interstitial fibrosis by decreasing the activation of the RAAS through renal changes in renin, angiotensin receptor 1 (ATR1) and ATR2 mRNAs levels and renal inflammation by decreasing renal inflammatory leucocytes (CD45), a desintegrin and metaloproteinase mRNA, transforming growth factor beta mRNA and protein, and maintaining E-cadherin mRNA levels. Calcitriol showed similar trends without significant changes in most of these biomarkers. CONCLUSIONS: Paricalcitol effectively attenuated the renal interstitial fibrosis induced by CRF through a combination of inhibitory actions on the RAAS, inflammation and epithelial/mesenchymal transition.

Original languageEnglish
Pages (from-to)793-803
Number of pages11
JournalNephrology Dialysis Transplantation
Volume36
Issue number5
DOIs
StatePublished - Apr 26 2021

Keywords

  • CKD
  • VDRAs
  • epithelial/mesenchymal-transition
  • inflammatory infiltration
  • renal fibrosis

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